KIGS data confirm male predominance in treated GH disorders

medwireNews: Twenty-five years of data from the Pfizer International Growth Study (KIGS) confirm that more boys than girls undergo treatment with growth hormone (GH).

The team found that boys accounted for 58% of the 83,803 children from Europe, the USA and Japan recorded in the KIGS database. This male predominance was seen for all geographical regions, but most strikingly for the USA. For example, among patients with idiopathic GH deficiency (IGHD), who comprised the largest proportion of patients overall, at 46.9%, the proportion of males was 77.2% in the USA, 69.6% in Japan and 68.1% in Europe.

Male predominance was observed for all major diagnostic categories, ranging from 71.4% for idiopathic short stature to 58.0% of children born small for gestational age. Yet their height was less severely affected than that of girls, with height standard deviation scores (SDSs) corrected for mid-parental height being significantly greater in boys than girls for all diagnoses – for example, at –2.24 versus –2.89 for those with congenital GHD. Boys were also significantly older than girls for most regions and diagnoses.

The KIGS data spans 1987 to 2012, over which time the overall predominance of boys treated with GH declined from 70% to 65% in Europe and from 73% to 68% in Japan, but remained stable at 77% in the USA.

Lead study author Michael Ranke (University Children’s Hospital, Tübingen , Germany) and colleagues say that even with all the information from KIGS, plus other large observational studies, it is not possible to determine whether the male predominance is a natural occurrence or if it is caused by referral and treatment bias.

But they stress: “There is a need for broader awareness of biases that are disadvantageous to girls, as they might be the very cause of the unfavorable changes that have been observed.

“At the same time, it can be argued that there is also a need for broader awareness of potentially unnecessary use of GH in boys.”

Despite the differences in gender, age and height SDS, patients had fairly similar peak stimulated GH levels across regions and diagnoses. The only significant differences were that European girls had lower levels than boys for acquired and congenital GHD, and US girls had lower levels than boys for congenital and idiopathic GHD.

“Given the level of complexity deriving from factors relating to diagnoses, the diversity of geographical regions, and the extended period of observation, it is rather remarkable that, on the global scale, there is considerable uniformity and consistency in the characteristics of prepubertal patients treated for different causes of shortness”, the researchers write in Hormone Research in Paediatrics.

The average GH dose used was generally highest in the USA, at 0.28 to 0.36 mg/kg per week, and lowest in Japan, at 0.17 to 0.19 mg/kg per week. Doses in Europe were intermediate, except for acquired GHD, for which the average dose used was just 0.18 mg/kg per week.

Over time, healthcare providers appeared to be treating less severely affected patients with higher GH doses; the average GH dose used increased in all regions, but patients’ corrected height SDSs rose significantly in the USA and Europe and their peak stimulated GH level rose significantly in Europe and Japan.